Research Interests
Regulation of intracellular hormone metabolism in target tissues, especially thyroid hormone metabolism
Thyroid hormones control growth, development and basal metabolic rate as well as most pathways involved in energy and structural metabolism.
Two essential trace elements, iodine and selenium, are involved in thyroid hormone biosynthesis. The amino-acid derived prohormone
L-thyroxine (T4), which is synthesized and secreted by the thyroid gland and circulates bound to specific hormone distributor proteins
in the blood, reaches its target cells by active transport across the cell membrane. Inside the cells, T4 is either activated to yield
the thyromimetically active hormone T3 or inactivated to reverse-T3 (rT3), a metabolite lacking hormone activity. T3 exerts its action
by binding to its receptors (TR), which are ligand-modulated transcription factors. Intracellular deiodination of T4, T3 and their
metabolites is catalysed by the deiodinase enzymes, members of the selenocysteine-containing protein family. Cellular uptake by specific
membrane transporters and intracellular metabolism of thyroid hormones by deiodinases is modulated by physiological, nutritive,
pharmacological and environmental factors, thus controlling and regulating availability of the hormonally active ligand T3 for TR
binding and modulation of gene expression. Among these factors are hormones, nutrients, cytokines, endocrine disrupters, etc.
In this regulatory hormone network currents aspects of our research address:
· Molecular mechanisms of hormone action
· Pituitary feedback regulation, especially interaction between thyroid axis and cytokines
· Hormonal regulation of development, growth, and cell differentiation
(These studies are partially integrated into the DFG-funded Graduate College 1208: Hormonal Regulation of Energy Metabolism, Body Weight and Growth; www.charite.de/graduiertenkolleg/GK1208)
· Hormonal and nutritional regulation of cancer, especially thyroid and gastrointestinal tumors
· As members of European (EURISKED) and German (Flavonet) research networks we investigate the (anti-)hormonal effects of flavonoids, other secondary metabolites of plants, nutritive polyphenols and endocrine disrupters on the development and function of the pituitary-thyroid-peripheral axis.
(www.eurisked.org; www.credocluster.info; www.flavonet.org).
· Other aspects of our research address the role of sex steroid hormones and their receptors during perinatal development with a focus on the brain-hypopthalamus-pituitary-gonad axis
Selected Recent Publications
(see köhrle / kohrle / koehrle / korhle in pubmed)
Schmutzler C, Schmitt TL, Glaser F, Köhrle J, Loos U 2002
The promoter of the human sodium/iodide-symporter gene responds to retinoic acid.
Mol. Cell. Endo. 189:145-155
Schomburg L, Schweizer U, Holtmann B, Flohe L, Sendtner M, Köhrle J. 2003
Gene disruption discloses role of Selenoprotein P in selenium delivery to target tissues.
Biochem J 370:397-402
Al-Taie OH, Seufert J, Karvar S, Adolph C, Mörk H, Scheurlen M, Köhrle J, Jakob F. 2003
Selenium supplementation enhances low selenium levels and stimulates glutathione peroxidase activity in peripheral blood and distal colon mucosa in past and present carriers of colon adenoma.
Nutr. & Cancer 46:125-130
Schmutzler C, Hoang-Vu C, Schreck R, Bienert K, Köhrle J 2004
Human thyroid carcinoma cell lines show different retinoid receptor repertoires and retinoid responses.
Europ J Endocrinol 150: 547-556
Friesema ECH, Grueters A, Biebermann H, Krude H, Moers A von, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MA, Kuiper GGJM, Balkassmi S, Uitterlinden AG, Köhrle J, Rodien P, Halestrap AP, Visser TJ (2004)
Severe X-linked psychomotor retardation caused by mutations in a thyroid hormone transporter.
Lancet 364: 1435-1437
Schmutzler C, Hamann I, Hofmann PJ, Kovacs G, Stemmler L, Mentrup B, Schomburg L, Ambrugger P, Grüters A, Seidlova-Wuttke D, Jarry H, Wuttke W, Köhrle J (2004)
Endocrine active compounds affect thyrotropin and thyroid hormone levels in serum as well as endpoints of thyroid hormone action in liver, heart and kidney.
Toxicology 205:95-102
Schweizer U, Streckfuß F, Pelt P, Carlson BA, Hatfield DL, Köhrle J, Schomburg L 2005
Hepatically-derived selenoprotein P is key a factor for kidney but not for brain selenium supply.
Biochem J 386(Pt 2):221-6
Schomburg L, Riese C, Michaelis M, Griebert E, Klein MO, Sapin R, Schweizer U, Köhrle J. 2006
Synthesis and metabolism of thyroid hormones is preferentially maintained in selenium deficient transgenic mice.
Endocrinology 147:1306-1313
Köhrle J, Jakob F, Contempré B, Dumont JE (2005)
Selenium, the Thyroid, and the Endocrine System.
Endocrine Reviews 26 (7):944–984.
Ganten D , Ruckpaul K, Köhrle J. (eds)
Molekulare Medizinische Grundlagen von Endokrinopathien II: Para- und Autokrine Regulation (2006)
|
Prof
Dr. Josef Köhrle
